Quercetin promotes cell apoptosis and inhibits the expression of MMP-9 and fibronectin via the AKT and ERK signalling pathways in human glioma cells

Neurochem Int. 2015 Jan:80:60-71. doi: 10.1016/j.neuint.2014.12.001. Epub 2014 Dec 3.

Abstract

Gliomas are the most common and malignant primary brain tumours and are associated with a poor prognosis despite the availability of multiple therapeutic options. Quercetin, a traditional Chinese medicinal herb, is an important flavonoid and has anti-cancer activity. Here, we evaluated whether quercetin could inhibit glioma cell viability and migration and promote apoptosis. The treatment of U87-MG glioblastoma and U251 and SHG44 glioma cell lines with different concentrations of quercetin inhibited cell viability in a dose-dependent manner. Wound healing assays indicated that quercetin significantly decreased glioma cell migration. β-galactosidase staining, DNA staining and Annexin V-EGF/PI double staining assays demonstrated that quercetin promoted cell senescence and apoptosis. In addition, the protein levels of p-AKT, p-ERK, Bcl-2, matrix metallopeptidase 9 (MMP-9) and fibronectin (FN) were significantly reduced following quercetin treatment. Therefore, we conclude that quercetin might inhibit the viability and migration and promote the senescence and apoptosis of glioma cells by suppressing the Ras/MAPK/ERK and PI3K/AKT signalling pathways. Quercetin might be a potential candidate for the clinical treatment of glioma.

Keywords: Apoptosis; Glioma; Matrix metallopeptidase 9 (MMP-9); Quercetin; p-AKT; p-ERK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Fibronectins / antagonists & inhibitors
  • Fibronectins / biosynthesis*
  • Gene Expression Regulation
  • Glioma / metabolism*
  • Humans
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Matrix Metalloproteinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Quercetin / pharmacology*

Substances

  • Fibronectins
  • Matrix Metalloproteinase Inhibitors
  • Quercetin
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 9